Aniridia is a congenital ocular syndrome characterized by iris hypoplasia and associated panocular anomalies which frequently results in blindness in affected individuals. The underlying etiology of this process is poorly understood, and no preventative treatment is available at present. Although the disease is frequently inherited in an autosomal dominant fashion with nearly one hundred percent penetrance, prenatal counselling is limited to probability estimates, with no definitive testing available. The goal of this study is to understand the etiology of aniridia on a molecular basis by seeking to identify and to clone the aniridia gene present on the p13 band of chromosome 11. A panel of patients with aniridia is being assembled for analysis with twenty-one newly developed DNA probes on chromosome 11p13. The patient DNA will be digested with rare cutter restriction endonucleases and separated by pulsed field gel electrophoresis. After transfer to reutilizable nylon membranes, the digested DNA will be hybridized with the probes seeking to identify microdeletions, rearrangements, or alterations in restriction fragment relationships in any of the panel members. If an altered fragment is found, a cloning strategy using cosmid or phage vectors will be employed. Additional probes within the candidate region for aniridia will be developed if an altered fragment is not found. To detect small deletions or alterations within the vicinity of a probe, patient panel DNA will also be digested with more frequent cutter enzymes and run with conventional gel electrophoresis techniques. Since there is evidence for a second aniridia gene on chromosome 2, linkage analysis on selected pedigrees with three affected generations will be performed using both newly developed chromosome 11p13 probes and existing chromosome 2p probes to better delineate the relative frequency of these two genetic alterations.